title: Gaba transporter SLC6A11 gene polymorphism associated with tardive dyskinesia.
abstract: BACKGROUND
  Gamma-aminobutyric acid (GABA) insufficiency has been reported to be related to the tardive dyskinesia (TD) susceptibility. Inada et al. (Pharmacogenet Genomics 2008;18:317-23) identified eight genes belonging to GABA receptor signaling pathway that may be involved in TD susceptibility by genome-wide screening and they replicated associations in an independent sample for polymorphisms in SLC6A11 (GABA transporter 3), GABRG3 (c-3 subunit of GABA-A receptor) and GABRB2 (β-2 subunit of GABA-A receptor). In this study, we tried to replicate their finding in a larger Korean sample and find if any of the genes was associated with the susceptibility to TD.
  
  
  METHODS
  We selected three polymorphisms in SLC6A11 (rs4684742), GABRG3 (rs2061051) and GABRB2 (rs918528) from the previous study. We carried out a case-control study (105 TD and 175 non-TD schizophrenic patients) to identify the association between the three candidate polymorphisms and susceptibility to TD and their epistatic interactions by using the multifactor dimensionality reduction (MDR) algorithm.
  
  
  RESULTS
  Among the three variants, SCL6A11 genotypes distribution showed a significant difference between the TD and non-TD patients (P = 0.049). However, GABRG3 and GABRB2 genotype distributions were not associated with TD (P = 0.268 and P = 0.976, respectively). Further, our analyses provided significant evidence for gene-gene interactions (SCL6A11, GABRG3 and GABRB2) in the development of TD. The odds ratio increased to 2.53 (CI = 1.515-4.217, P = 0.0003) when the genetic susceptibility to TD was analyzed with the three genes considered altogether through MDR approach.
  
  
  CONCLUSIONS
  These results suggest that GABA receptor signaling pathway was associated with the increased susceptibility to TD in Korean schizophrenic patients.
authors.affiliation: Woo-Young Son, Department of Psychiatry, Korea University College of Medicine , Seoul , South Korea , and Department of Biology, Cornell University College of Arts and Sciences , NY 14850 , USA.
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Son
authors.forename: Heon-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ho-Kyoung
authors.initials: HK
authors.lastname: Yoon
authors.forename: Seung-Gul
authors.initials: SG
authors.lastname: Kang
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Yang
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Hyonggin
authors.initials: H
authors.lastname: An
authors.forename: Han-Kyu
authors.initials: HK
authors.lastname: Seo
authors.forename: Leen
authors.initials: L
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D056910:Republic of Korea; D012559:Schizophrenia / Q000150:complications
chemical_list: D017931:DNA Primers; D050485:GABA Plasma Membrane Transport Proteins; C493416:SLC6A11 protein, human